Regional gray matter reduction correlates with subjective quality of life in schizophrenia

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Abstract

Subjective quality of life (QOL) has been recognized as an important consideration in schizophrenia. Several symptoms and neurocognitive functions were shown to be correlated with subjective QOL; however its determinants are not well understood. In this study, we investigated the association between brain structural abnormalities and subjective QOL in patients with schizophrenia. Forty-five schizophrenia patients and 48 age, sex, and education-matched healthy participants underwent magnetic resonance imaging (MRI), and the Schizophrenia Quality of Life Scale (SQLS) was used to rate subjective QOL. We performed voxel-based morphometry (VBM) to investigate regional brain alterations. Relative to normal controls, schizophrenia patients exhibited gray matter reductions mainly in the frontal and temporal regions. Worse psychosocial subscale of SQLS was associated with gray matter (GM) reduction in the right dorsolateral prefrontal cortex (DLPFC), and worse motivation/energy subscale was associated with gray matter reduction in the left superior frontal sulcus, left parahippocampal gyrus, and the left inferior temporal gyrus. The correlation between DLPFC GM volume and psychosocial subscale of SQLS disappeared after controlling for severity of psychopathology, while the other correlations remained significant when controlled by demographic and clinical variables. Combining imaging techniques with psychosocial methods would help to elucidate those factors that are associated with QOL.

Introduction

Quality of life (QOL) is an important consideration for patients with schizophrenia (Hofer et al., 2005). QOL is defined as a person's sense of well-being, life satisfaction and health status (Lehman, 1997). Previous studies have investigated predictors of QOL in schizophrenia, and several studies reported sociodemographic factors, depressive mood, and psychiatric symptoms as important determinants for QOL (Jin et al., 2001; Hofer et al., 2005; Aki et al., 2008; Yamauchi et al., 2008; Narvaez et al., 2008).

Among the psychiatric symptoms, severity of both positive symptoms (Gaite et al., 2002; Ritsner, 2003; Thornicroft et al., 2004) and negative symptoms (Packer et al., 1997; Heslegrave et al., 1997; Aksaray et al., 2002) have been associated with worse QOL. Although, previous studies show some inconsistency, recent meta-analysis found weak but significant correlations between positive and negative symptom levels and QOL (Eack and Newhill, 2007).

Brain magnetic resonance imaging (MRI) studies have demonstrated multiregional gray matter (GM) reductions in patients with schizophrenia (Haijma et al., 2012; Suzuki et al., 2005). Voxel-based morphometry (VBM; Ashburner and Friston, 2000) is an automated imaging-analysis method for exploring regional GM alterations in the whole brain. Recent meta-analyses of VBM studies of patients with schizophrenia showed GM reductions in such regions as the medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, superior temporal gyrus (STG), insula, parahippocampal gyrus, amygdala, thalamus, and striatum (Ellison-Wright et al., 2008; Glahn et al., 2008). Some of these regional GM alterations were found to be related to symptom severity in schizophrenia patients. For instance, a large sample VBM study (Koutsouleris et al., 2008) reported associations between the abnormalities in the perisylvian region and positive symptoms, and a meta-analysis (Bora et al., 2011) reported an association between the abnormalities in the medial frontal gyrus/orbitofrontal cortex and negative symptoms.

Thus, the previous studies suggest associations between QOL and symptoms, and between GM and symptoms. Our interest in this study was to explore the more detailed nature of the interrelationship among QOL, symptoms, and GM pathology, using VBM. We expected associations among some aspects of QOL, positive symptoms, and perisylvian GM pathology, and associations among other QOL aspects, negative symptoms, and prefrontal GM pathology.

Section snippets

Participants

The schizophrenia group comprised 45 patients (25 men and 20 women, 42 right-handed and 3 left-handed) who were referred to the Department of Neuropsychiatry, Kyoto University Hospital. Each patient fulfilled the criteria for schizophrenia based on the Structural Clinical Interview for DSM-IV (SCID). Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987). All patients were receiving antipsychotic medication (first-generation [n = 4],

Demographic and clinical data

Table 1 shows demographic and clinical information. The estimated VIQ and PIQ were significantly lower in patients with schizophrenia than in controls. However, there was no significant difference in demographics (age, gender, handedness, education level) between patients with schizophrenia and controls.

Correlational analysis

There were no significant correlations between the psychosocial subscale score of SQLS and demographic variables, i.e. age, gender, education, and estimated VIQ/PIQ, in the patient group.

Discussion

This is the first study, to our knowledge, to investigate the relationship between subjective QOL, symptoms and brain volume in patients with schizophrenia, using the VBM technique. Our study revealed that volume reductions in some cortical areas are correlated with lower QOL. This is an exploratory study without multiple comparison correction, and thus caution should be taken in interpreting these results, although such a combination of imaging and psychosocial assessments would be useful to

Role of funding source

This work was supported by Grant-in-Aid for Scientific Research B (23390290), S (22220003), a Grant-in-Aid for Young Scientist A (23680045), B (23791329) and on Innovative Areas (23118004, 23120009) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Takeda Science Foundation, The Uehara Memorial Foundation and Senshin Medical Research Foundation. Schizophrenia Research Group, Research Group for Schizophrenia sponsored by Astellas Pharma Inc.

Contributors

JM, MY and TM designed the study and wrote the protocol under the supervision of HF. SU and TU managed the literature searches and analyses. SU, JM, MY, KH, HF, RK, SF, YT, MK and AS collected the data. NS supervised the MRI data acquisition and processing. SU undertook the statistical analysis under the supervision of HF, HT, and TM. SU wrote the first draft of the manuscript, and contributed substantially to all subsequent drafts of the manuscript. All authors contributed to and have approved

Conflict of interest

All authors declare that they have no conflict of interest.

Acknowledgment

We would like to thank Prof. Rumi Tanemura, and most of all, to the patients and volunteers for participating in the study.

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